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A. Caicedo, D.G. Espinosa–Heidmann, Y. Pina, E.P. Hernandez, S.W. Cousins; Blood–derived macrophages infiltrate the retina and activate Muller glial cells in choroidal neovascularization (CNV). . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1791. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Macrophages, the main effector cells of innate immunity, have recently been demonstrated to contribute to the pathogenesis of CNV. Microglia, the tissue resident macrophages of the brain and retina, have been implicated in traumatic and degenerative conditions of the retina. However, no information is available for retinal macrophages or microglia in age–related macular degeneration, and the contribution of blood–derived macrophages to any retinal condition is unknown. In this study, we examined the relative role of recruited blood–derived macrophages versus resident microglia in the retina associated with CNV. Methods: Chimeric GFP mice were generated by reconstituting C57/BL/6 mice with bone marrow from GFP transgenic mice. Laser–induced CNV was induced one month after bone marrow transplant. Immunofluorescence staining was used to examine cross–sections and flatmount preparations of the retina associated with CNV. Tissue resident monocytes (F4/80+/GFP–) and blood–derived monocytes (double positive) were enumerated at various times post CNV. Results: Macrophage density increased by 270% in the retina, but macrophages remained spatially localized to the retina associated with CNV. No increase was observed in the unaffected, adjacent retina. Almost all of the increase was explained by GFP–labeled blood–derived macrophages; 85% of the macrophages were GFP–labeled. Many GFP–labeled cells co–localized with activated Muller cells expressing c–fos or pERK. Depletion of blood–derived macrophages with liposome–encapsulated clodronate prevented retinal macrophage infiltration and diminished the density of activated Muller cells by 50%. Conclusions: Macrophage–mediated inflammation contributes to retinal degeneration in CNV where they appear to activate Muller cells. Most of the macrophages are blood–derived and not tissue resident microglia.
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